Preclinical and clinical studies have shown that Photodynamic Therapy (PDT) augments the host immune response. We have made that novel discovery that the direct effects of Photofrin-PDT on tumor cells are sufficient to stimulate the host immune system. The overall goal of this project is understand how PDT enhances the immunogenicity of tumor cells, in vivo and in vitro. We hypothesize the PDT treatment of tumor cells, in vivo or in vitro enhances their ability to be recognized by the host immune system. We have shown that increased tumor immunogenicity can be correlated with an ability to mature and activate antigen-presenting cells and we hypothesize that Photofrin-PDT stimulates the expression of immune mediators that are able to increase the activity of antigen-presenting cells. In Specific Aim I of this proposal we will identify the factor(s) present in Photofrin-PDT generated tumor cell lysates that activate dendritic cells. We further hypothesize that the secretion of immune enhancing factors is dependent upon the initial immunogenicity of the tumor and the type of PDT regimen employed. This hypothesis will be tested in Specific Aim II. In Specific Aim III we will test whether clinical PDT, like preclinical PDT, augments the anti-tumor immune response. The studies outlined in this project will further our knowledge of how PDT affects the host immune response. An understanding of these mechanisms will potentially allow for the development of an optimal "immune enhancing" PDT protocol, which may provide a means of improving the patients ability to combat tumor and/or metastases outside the treatment field.